Kazuto Kishimoto

Endoscopic and radiographic features of gastrointestinal involvement in vasculitis

Vasculitis is an inflammation of vessel walls, followed by alteration of the blood flow and damage to the dependent organ. Vasculitis can cause local or diffuse pathologic changes in the gastrointestinal (GI) tract. The variety of GI lesions includes ulcer, submucosal edema, hemorrhage, paralytic ileus, mesenteric ischemia, bowel obstruction, and life-threatening perforation.The endoscopic and radiographic features of GI involvement in vasculitisare reviewed with the emphasis on small-vessel vasculitis by presenting our typical cases, including Churg-Strauss syndrome, Henoch-Schönlein purpura, systemic lupus erythematosus, and Behçets disease. Important endoscopic features are ischemic enterocolitis and ulcer. Characteristic computed tomographic findings include bowel wall thickening with the target sign and engorgement of mesenteric vessels with comb sign. Knowledge of endoscopic and radiographic GI manifestations can help make an early diagnosis and establish treatment strategy.

Endoscopic and histopathological features of gastrointestinal amyloidosis

Amyloidosis is a rare disorder, characterized by the extracellular deposition of an abnormal fibrillar protein, which disrupts tissue structure and function. Amyloidosis can be acquired or hereditary, and systemic or localized to a single organ, such as the gastrointestinal (GI) tract. Clinical manifestations may vary from asymptomatic to fatal forms. Primary amyloidosis (monoclonal immunoglobulin light chains, AL) is the most common form of amyloidosis. AL amyloidosis has been associated with plasma cell dyscrasias, such as, multiple myeloma. Secondary amyloidosis is caused by the deposition of fragments of the circulating acute-phase reactant, serum amyloid A protein (SAA). Common causes of AA amyloidosis are chronic inflammatory disorders. Although GI symptoms are usually nonspecific, histopathological patterns of amyloid deposition are associated with clinical and endoscopic features. Amyloid deposition in the muscularis mucosae, submucosa, and muscularis propria has been dominant in AL amyloidosis, leading to polypoid protrusions and thickening of the valvulae conniventes, whereas granular amyloid deposition mainly in the propria mucosae has been related to AA amyloidosis, resulting in the fine granular appearance, mucosal friability, and erosions. As a result, AL amyloidosis usually presents with constipation, mechanical obstruction, or chronic intestinal pseudo-obstruction while AA amyloidosis presents with diarrhea and malabsorption Amyloidotic GI symptoms are mostly refractory and have a negative impact on quality of life and survival. Diagnosing GI amyloidosis requires high suspicion of evaluating endoscopists. Because of the absence of specific treatments for reducing the abundance of the amyloidogenic precursor protein, we should be aware of certain associations between patterns of amyloid deposition and clinical and endoscopic features.

Fucoidan enhances intestinal barrier function by upregulating the expression of claudin-1

AIM To evaluate the protective effects of fucoidan on oxidative stress-induced barrier disruption in human intestinal epithelial cells. METHODS In Caco-2 cell monolayer models, the disruption of barrier function by oxidative stress is mediated by H₂O₂. The integrity of polarized Caco-2 cell monolayers was determined by measuring the transepithelial resistance (TER) and permeability was estimated by measuring the paracellular transport of FITC-labeled 4-kDa dextran (FD4). The protective effects of fucoidan on epithelial barrier functions on polarized Caco-2 cell monolayers were evaluated by TER and FD4 flux. The expression of tight junction (TJ) proteins was assessed using reverse-transcription polymerase chain reaction (RT-PCR) and immunofluorescence staining. RESULTS Without H₂O₂ treatment, fucoidan significantly increased the TER compared to control (P < 0.05), indicating a direct enhancement of intestinal epithelial barrier function. Next, H₂O₂ disrupted the epithelial barrier function in a time-dependent manner. Fucoidan prevented the H₂O₂-induced destruction in a dose-dependent manner. Fucoidan significantly decreased H₂O₂-induced FD4 flux (P < 0.01), indicating the prevention of disruption in paracellular permeability. RT-PCR showed that Caco-2 cells endogenously expressed claudin-1 and -2, and occludin and that H₂O₂ reduced the mRNA expression of these TJ proteins. Treatment with fucoidan attenuated the reduction in the expressions of claudin-1 and claudin-2 but not occludin. Immunofluorescence staining revealed that the expression of claudin-1 was intact and high on the cell surface. H₂O₂ disrupted the integrity of claudin-1. Treatment with fucoidan dramatically attenuated the expression of claudin-1. CONCLUSION Fucoidan enhanced intestinal epithelial barrier function by upregulating the expression of claudin-1. Thus, fucoidan may be an appropriate therapy for the treatment of inflammatory bowel diseases.

Diagnosis of intestinal tuberculosis using a monoclonal antibody to Mycobacterium tuberculosis

AIM To investigate the utility of immunohistochemical (IHC) staining with an antibody to Mycobacterium tuberculosis (M. tuberculosis) for the diagnosis of intestinal tuberculosis (TB). METHODS We retrospectively identified 10 patients (4 males and 6 females; mean age = 65.1 ± 13.6 years) with intestinal TB. Clinical characteristics, including age, gender, underlying disease, and symptoms were obtained. Chest radiograph and laboratory tests, including sputum Ziehl-Neelsen (ZN) staining, M. tuberculosis culture, and sputum polymerase chain reaction (PCR) for tubercle bacilli DNA, as well as Tuberculin skin test (TST) and QuantiFERON-TB gold test (QFT), were examined. Colonoscopic records recorded on the basis of Satos classification were also reviewed, in addition to data from intestinal biopsies examined for histopathological findings, including hematoxylin and eosin staining, and ZN staining, as well as M. tuberculosis culture, and PCR for tubercle bacilli DNA. For the present study, archived formalin-fixed paraffin-embedded (FFPE) intestinal tissue samples were immunohistochemically stained using a commercially available species-specific monoclonal antibody to the 38-kDa antigen of the M. tuberculosis complex. These sections were also stained with the pan-macrophage marker CD68 antibody. RESULTS From the clinical data, we found that no patients were immunocompromised, and that the main symptoms were diarrhea and weight loss. Three patients displayed active pulmonary TB, six patients (60%) had a positive TST, and 4 patients (40%) had a positive QFT. Colonoscopic findings revealed that all patients had type 1 findings (linear ulcers in a circumferential arrangement or linear ulcers arranged circumferentially with mucosa showing multiple nodules), all of which were located in the right hemicolon and/or terminal ileum. Seven patients (70%) had concomitant healed lesions in the ileocecal area. No acid-fast bacilli were detected with ZN staining of the intestinal tissue samples, and both M. tuberculosis culture and PCR for tubercle bacilli DNA were negative in all samples. The histopathological data revealed that tuberculous granulomas were present in 4 cases (40%). IHC staining in archived FFPE samples with anti-M. tuberculosis monoclonal antibody revealed positive findings in 4 patients (40%); the same patients in which granulomas were detected by hematoxylin and eosin staining. M. tuberculosis antigens were found to be mostly intracellular, granular in pattern, and primarily located in the CD68(+) macrophages of the granulomas. CONCLUSION IHC staining with a monoclonal antibody to M. tuberculosis may be an efficient and simple diagnostic tool in addition to classic examination methods for the diagnosis of intestinal TB.

Systemic lupus erythematosus complicated with protein-losing enteropathy: a case report and review of the published works.

A 45‐year‐old man was referred to our hospital with a history of multiple erythematous skin lesions of several months’ duration. Blood examination revealed extreme hypoproteinemia and hypoalbuminemia, as well as the presence of antinuclear antibodies. A skin biopsy specimen showed liquefaction degeneration at the dermoepidermal junction and dense lymphocyte and neutrophil infiltration around the vessels and appendages in the upper and middle dermis. Chest X‐ray and computed tomography showed a pleural effusion and thoracic paracentesis revealed a mononuclear cell‐dominant cell infiltration, suggestive of serositis. Technetium‐99m (99mTc)‐labeled human serum albumin scintigraphy and α1‐antitrypsin clearance revealed protein leakage along the digestive tracts from the stomach to the jejunum. From the above findings, the patient was diagnosed with systemic lupus erythematosus (SLE) complicated by protein‐losing enteropathy (PLE). Treatment with oral prednisolone significantly improved his clinical symptoms and hypoalbuminemia. This case highlighted the utility of 99mTc‐labeled human serum albumin scintigraphy and α1‐antitrypsin clearance in the diagnosis of PLE. We also present a published work review on PLE associated with connective tissue disease revealing a relatively higher prevalence in patients of Asian ethnicity, including Japanese.

Impending megacolon: small bowel distension as a predictor of toxic megacolon in ulcerative colitis

We have read with great interest the recent excellent review by Di Sabatino et al. [1] on ulcerative colitis (UC). We fully agree with their description that toxic megacolon is a life-threatening complication in severe UC, and that a standard plain X-ray study is useful to evaluate the degree of intestinal distension. In clinical settings, delay of surgery sometimes bears a poor prognosis when patients may not fulfill the clinical criteria for toxic megacolon by Jalan et al. [2] or definitive colonic dilatation. We recently experienced a case of ‘impending’ megacolon in a patient with UC, highlighting small bowel distension as a predictor of toxic megacolon. A 27-year-old man with UC presented with sudden onset of severe abdominal pain after 5 weeks’ duration of relapse with hematochezia. He had experienced multiple relapses of pancolitis and was being treated with 750 mg of oral mesalazine three times a day for over 6 years since the first presentation of colitis. On examination, the temperature was 37.6 C. Abdominal examination revealed a distended and tender abdomen with marked rebound and hypoactive bowel sounds. The clinical activity index was elevated up to 19. Laboratory tests showed an increased white blood cell count of 17,400/lL and a C-reactive protein of 8.36 mg/dL. A supine abdominal X-ray study (Fig. 1) showed a notable dilatation of the small intestine with a maximum internal diameter exceeding 4 cm (arrows) as well as indistinct colonic distension (arrowheads). He was diagnosed as having impending megacolon of UC, and therefore underwent subtotal colectomy with end ileostomy. Histopathological examination revealed severe transmural inflammation of the colon. He had an uneventful post-surgical course. Toxic megacolon, a life-threatening complication of UC and diverse colitis, is defined as nonobstructive hypotonic dilatation of the colon, classically exceeding 5.5 cm in diameter in the transverse colon on supine abdominal X-ray [3]. The pathogenesis for megacolon seems to be the excessive colonic production of inflammatory mediators that inhibit colonic motility and nitric oxide, as the key nonadrenergic, noncholinergic neurotransmitter induces colonic muscle relaxation. Recent studies indicate that the finding of persistent small bowel distension on plain abdominal radiograph characterizes a subgroup of patients at high risk for the development of toxic megacolon and multiorgan dysfunction, termed ‘impending’ megacolon [4, 5]. Gaseous distension in the uninflamed stomach and small intestine may precede colonic dilatation presumably due to the increased release of the above inflammatory mediators. The distension can result from the activation of extrinsic intestine–intestinal inhibitory reflexes, which induce paralytic ileus [5]. In conclusion, although the clinical entity of ‘impending’ megacolon has not been established yet, we highlight small bowel distension as a reliable predictor of toxic megacolon, called ‘impending’ A. Hokama (&) K. Kishimoto J. Fujita Department of Infectious, Respiratory and Digestive Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan e-mail: hokama-a@med.u-ryukyu.ac.jp

Chronic intermittent vomiting after scoliosis surgery

A 12 year old girl presented with an 18 month history of intermittent postprandial vomiting …

Appendiceal Orifice Inflammation in Ulcerative Colitis

A 44-year-old man was diagnosed with distal ulcerative colitis (UC) when he had hematochezia at the age of 34. He had had a few relapses on maintenance oral mesalazine. He desired a total colonoscopy in the clinical remission. Physical examination showed no abnormalities and routine laboratory tests were normal. Colonoscopy disclosed the appendiceal orifice inflammation (AOI) with reddish and friable mucosa and mucopus (Fig. 1). The remaining colorectum showed no inflammation. He remains well during the follow-up. Since Cohen et al. first coined ‘‘ulcerative appendicitis’’ [1], AOI is uncommon but has increasingly been recognized in patients of distal UC. UC classically extends proximally from the rectum without skip lesions. Isolated AOI has been more frequently observed in patients with less extensive UC and is unlikely the result of patchy improvement due to treatments. The human appendix has long been recognized as a vestigial remnant. Although the pathogenesis of UC has not been fully clarified, clinical evidence has revealed the protective role of appendicectomy on onset and severity of UC [2, 3], indicating the appendix as a priming site for UC [4]. Experimental studies of murine models have also shown that the appendix may serve a central role in antigen sampling and immunological signaling [5]. Therefore, further studies of AOI may unveil not only its clinical implication but also the immunopathogenesis of UC. References

Endoscopic clipping in the lower gastrointestinal tract

Endoscopic clipping has been established as a safe and effective method for the treatment of nonvariceal upper gastrointestinal bleeding in numerous randomized studies. Recently, clipping has been applied to various lesions in the lower gastrointestinal tract, including diverticular bleeding, postpolypectomy bleeding, and repair of perforations with successful outcomes. We review the safety and efficacy of this maneuver for the management of diseases in the lower gastrointestinal tract.

Colonic stricture with filiform polyposis in Crohn's disease

A 41-year-old man with a 5-year history of Crohns disease presented with abdominal distention, right lower quadrant pain and weight loss for 4 weeks. On physical examination, the abdomen was distended with right lower quadrant tenderness. Plain radiograph of the abdomen disclosed marked dilation of the ascending colon due to a stricture at the hepatic flexure and intraluminal polypoid filling defects that suggested the presence of postinflammatory polyps (figure 1). Colonoscopy failed to disclose the precise cause …